DESCRIPTION: How natural cation-conducting channels function in vivo is one of the most important and vigorously studied areas of modern science. In the first stage of this project, the goal was to develop a synthetic, cation-conducting, model channel system that could be used to probe cation channel function. Such a system has been designed, synthesized, and fully characterized. Structural variations in the model system afford a comprehensible structure-activity relationship. Using this functional model system, the phase of the project described in this proposal will deal with the essential issue of how cations are conducted and how the cation selectivity profile is achieved. The cation conduction and selectivity studies will all be conducted in lipid bilayer membranes. Such cation selectivity information will enhance in a fundamental way the understanding of how cations are bound, selected, gated, and released within bilayers. A collateral goal is to use our model system to discover how known, single-strand, transmembrane proteins can be stabilized within a bilayer and how association of monomers can be fostered, perhaps to form a pore with selectivity different from that exhibited by an individual channel segment. The work proposed here will be conducted on systems simpler than those found in nature (natural protein channels) but specific chemical questions will be asked, the answers to which are relevant to all biological channel-formers.